. 2023 Aug 5;15(15):3980. doi: 10.3390/cancers15153980

Table 2.

In vitro studies of plant-based bioactive compounds in lung cancer.

Phytochemicals	Cell Lines	Conc.	IC₅₀	Anticancer Effect	Mechanisms	References
Alkaloids
Acutiaporberine	95-D	0.003 µM	Not reported	Increased cell death	↑Bak/Bcl-2 ratio	[174]
β-Carboline	A549	1.80 μM	Not reported	Showed cytotoxic activity	↑ERK1/2; ↓Akt/mTOR	[175]
Berberine	A549 and H1299	25, 50, 75, and 100 µM	Not reported	Suppressed tumor cell growth and increased cell death	↓Bcl-2; ↑caspase-3; ↑Bax	[176]
Homoharringtonine	A549 and H1975	2–4 μM	3.7 μM(A549) and 0.7 μM (H1975)	Inhibited tumor cell metastasis	↓JAK1/STAT3	[177]
Homoharringtonine	A549 and H1299	2 µM	Not reported	Inhibited tumor cell growth and metastasis	↓KRAS; ↓ERK; ↓Akt; ↓STAT3; ↓CDK4; ↓CDK6; ↓p21; ↓RB	[178]
Indole-3-carbinol	H1299	400 μM	449.5 μM	Increased cell death and oxidative stress	↑ROS; ↑caspase-3; ↑caspase-7; ↑caspase-9; ↓Bcl-2	[179]
Melosine B	A549	0.064, 0.32, 1.6, 8, and 40 µM	8.1 μM	Exhibited cytotoxicity and increased cell death	Not reported	[180]
Piperine	A549	50, 100, and 200 μg/mL	122 μg/mL	Inhibited tumor cell growth	↑Bax/Bcl-2 ratio; ↑caspase-3; ↑caspase-9	[181]
Piperine	A549	20, 40, 80, 160, and 320 µM	198 µM	Inhibited tumor cell migration and invasion	↓ERK 1/2; ↓SMAD 2; ↓TGF-β	[182]
Solamargine	H1650, H1975, PC9, A549, and H1299	2, 4, and 6 µM	Not reported	Reduced tumor cell growth and increased DNA damage	↑ERK1/2; ↓prostaglandin E2; ↓DNMT1; ↓c-Jun	[183]
Vallesiachotamine and iso-vallesiachotamine	H1299	12.5, 25, 50, 100, and 200 μM	4.24 μM (vallesiachotamine) and 3.79 μM (iso-vallesiachotamine)	Suppressed tumor cell growth and caused DNA damage	↑Apoptosis	[184]
Phenolics
Acacetin	A549	1–5 μM	Not reported	Decreased tumor cell growth and viability	↓Activator protein-1; ↓NF-κB; ↓MLK3; ↓MAPK3/6; ↓p38a; ↓MAPK	[185]
Apocynin	A549	50–1000 μM	890 μM	Decreased tumor cell growth and enhanced cell death	↓Cellular microtubule network	[186]
Baicalein	A549 and H1299	2.5, 10, and 40 μM	Not reported	Reduced tumor cell growth, metastasis, and invasion	↓Cellular ezrin S-nitrosylation	[187]
Batatasin III	H460	25–100 μM	Not reported	Inhibited tumor cell migration and invasion	↓EMT; ↓N-cadherin; ↓vimentin; ↓Akt; ↑E-cadherin	[188]
Caffeic acid	A549	50–1000 μM	Not reported	Reduced tumor cell growth	↓Superoxide level	[189]
Cardamonin	A549 and H460	40 μM	Not reported	Decreased tumor cell growth and increased cell death	↑Caspase-3; ↑Bcl-2; ↑Bax; ↑cyclin D1; ↓CDK4; ↓PI3K; ↓Akt; ↓mTOR	[190]
Cardamonin	A549	0.1, 1, 10, and 30 μM	Not reported	Reduced tumor cell growth and enhanced cell death	↓mTOR; ↓DNA synthesis; ↓p70S6K	[191]
Cardamonin analogs	A549 and NCI-H460	0.05–100 µM	0.445 µM (DHC) and 0.166 µM (DHMC)	Inhibited tumor cell growth	↓NF-κB	[192]
Casticin	A549	1, 5, 10 µM	14.3 µM	Suppressed tumor cell growth and enhanced cell death	↓IL-6; ↓COX-2; ↓MAPK; ↓NF-κB; ↓p65; ↓chemokine gene	[193,194]
Chrysin	A549	25, 50, and 75 µg/mL	55.72 μg/mL	Inhibited tumor cell growth and increased cell death	↑Bax; ↓Bcl-2; ↑caspase-3	[195]
Curcumin	A549	10 µM	Not reported	Decreased tumor cell growth and enhanced cell death	↓Prosurvival antiapoptotic factors; ↓EGFR	[196]
	A-549	10–50 µM	Not reported	Caused DNA damage and G2/M phase cell cycle arrest	↑Caspase-3-induced apoptosis; ↑DNA damage; ↑ER stress	[197]
	NCI-H460	30 μM	Not reported	Suppressed tumor cell growth and enhanced cell death	↑Caspase-3; ↑caspase-8; ↓cyclin-dependent kinase 1	[198]
	CL1–5	1–20 μM	Not reported	Inhibited tumor cell growth and metastasis	↑Activator protein-1; ↓E-cadherin;	[199]
	PC-9	50 μM	Not reported	Enhanced DNA damage, cell death and suppressed tumor cell growth	↑DNA damage; ↓Bcl-2; ↓cyclin D1; ↓CDK2; ↓CDK4; ↓CDK6	[200]
	NCI-H292	5–40 μM	15 μM	Increased cell death and inhibited tumor cell growth	↑Bax; ↑caspase-3; ↑caspase-7	[201]
p-Coumaric acid	A549, NCI-H1299, and HCC827	10–100 µg/mL	37.73 μg/mL (A549); 50.6 μg/mL (H1299); 62.0 μg/mL (HCC827)	Increased cell death	↑Bax; ↓Bcl-2; ↑caspase-3; ↑caspase-9	[202]
p-Coumaric acid	H1993	50–100 μM	Not reported	Reduced tumor cell growth and viability	↓Resistance of tyrosine kinase inhibitor	[203]
EGCG	A549 and H1299	20–300 μM	86.4 µM (A549) and 80.6 µM (H1299)	Inhibited tumor cell proliferation and induced apoptosis	↓NF-κB	[204]
	H1299 and CL-13	10–100 µM	174.9 µM(H1299) and 181.5 µM (CL-13)	Reduced tumor cell proliferation	↑ROS; ↓ NF-κB	[205]
	A549	10, 25, 50, and 100 µM	Not reported	Decreased tumor cell growth	↓Nicotine-induced Akt; ↓ERK1/2	[206]
	A549	12.5, 25, and 50 μM	25 μM	Suppressed tumor cell growth, invasion, migration and increased G2/M phase cell cycle arrest	↑Bax/Bcl-2 ratio	[207]
	A549	0.5 μM	Not reported	Decreased tumor cell growth and increased oxidative stress	↑ Nrf2; ↑ROS	[208]
	A549 and NCI-H23	0.05–500 µM	Not reported	Reduced etoposide resistance and tumor cell growth	↑Nrf2; ↑ROS;	[209]
	H1299, H460 and A549	40 µM	Not reported	Decreased tumor cell growth	↑miR-210	[210]
	H1299 and A549	10, 20, and 40 µM	Not reported	Induced apoptosis	↓PI3K/Akt	[211]
EGCG and luteolin	A549 and H460	30 µM (EGCG) and 10 µM (luteolin)	Not reported	Induced apoptosis	↑p53 mitochondrial translocation; ↑DNA damage	[212]
EGCG and theaflavins	NCI-H460	100µM	Not reported	Inhibited tumor cell proliferation and promoted apoptosis	↑p53; ↓Bcl-2	[213]
Ferulic acid	A549	50–1000 μM	Not reported	Enhanced oxidative stress and decreased cell viability	↓Superoxide anion	[189]
Fisetin	A549	5–20 μM	Not reported	Decreased cell viability and increased cell death	↓PI3K/Akt; ↓mTOR	[214]
	NCI-H460	75 µg/mL	Not reported	Inhibited tumor cell growth and viability	↓β-cell lymphoma-2; ↑Bcl-2; ↑caspase-9; ↑caspase-3	[215,216]
	HCC827-ER	10, 20, 40, 60, 80, 100, 120 μM	Not reported	Inhibited tumor cell growth, viability and increased cell death	↓Axl; ↓MAPK; ↓Akt	[217]
Gallic acid	Calu-6 and A549	10–200 μM	10–50 µM (Calu-6); 100–200 µM (A549)	Inhibited tumor cell growth and enhanced oxidative stress	↓GSH; ↑ROS	[218]
Gallic acid	H1975 and H1993	50 μM	Not reported	Increased cell death	↓Src-mediated STAT3; ↓Bcl-2; ↓cyclin D; ↓NF-κB; ↓IL-6	[219]
Genistein	A549	10 μM	Not reported	Inhibited tumor cell growth and enhanced cell death	↑Caspase-3	[220]
	H3255, H1650, and H1781	25 μM	Not reported	Decreased tumor cell growth and increased cell death	↓DNA binding of NF-κB; ↓COX-2; ↓pAkt; ↓EGFR; ↓PGE2	[221]
	SPC-A-1	20–40 μM	Not reported	Reduced tumor cell growth and increased cell death	↓Bcl-2	[222]
	H460	15–30 μM	Not reported	Suppressed tumor cell growth and increased cell death	↓NF-κB	[223]
Gigantol	A549	25, 50, and 100 µM	Not reported	Inhibited tumor cell growth and increased cell death	↓Ki-67; ↓Bcl-2; ↑Bax; ↑Wnt/β-catenin	[224]
	H460	50 μM	Not reported	Increased tumor cell death	↓EMT	[225]
	H460	20–200 µM	Not reported	Reduced tumor cell proliferation, migration, and invasion	↓PI3K/Akt/mTOR; ↓JAK/STAT	[226]
Hesperidin	A549 and NCI-H358	5–50 μM	50 μM	Increased cell death	↑Apoptosis; ↑mitochondrial disruption; ↑caspase-3; ↑NF-κB	[227]
Hesperidin	H1993	5–100 μM	Not reported	Decreased cell viability and enhanced cell death	↓Resistance of tyrosine kinase inhibitor	[203]
Honokiol	A549 and 95-D	5, 10, or 20 μM	Not reported	Increased cell death	↑Bax; ↑caspase-9; ↑PERK; ↑ER stress; ↓Bcl-2	[228,229]
Honokiol	A549 and LL/2	10–50 μM	21.1 μM	Reduced tumor cell growth and increased cell death	↓VEGF-A	[230]
Mono-demethylated polymethoxyflavones	H1299	1–30 µM	16.5 μM	Increased cell death	↓iNOS; ↓COX-2; ↓Mcl-1; ↑caspase-3; ↑PARP cleavage	[231]
Indolyl-chalcone derivatives	A549	2.5 μM and 5 μM	2.46 μM	Suppressed tumor cell growth	↑Nrf-2/HO-1	[232]
Isorhamnetin	A549	8 μM and 16 μM	Not reported	Increased cell death and mitochondrial dysfunction	↑Caspase-3	[233]
Isorhamnetin	A549	25 μM	Not reported	Enhanced mitochondrial dysfunction, cell death and decreased tumor cell growth	↑Caspase-3; ↑PARP	[234]
Kaempferol	A549	10–140 μM	72 μM	Inhibited epithelial–mesenchymal transition and increased cell death	↑EMT; ↓E-cadherin; ↓vimentin	[235]
	A549	25 μM	Not reported	Inhibited tumor cell growth and viability	↓E-Cadherin; ↓vimentin ↓Akt1-mediated phosphorylation; ↓TGF-β1	[236]
	H460	30, 50, and 80 μM	50 μM	Enhanced oxidative stress and cell death	↑Caspase-3; ↑AIF	[237]
Kurarinone	H460	2 µg/mL	5.8 µg/mL	Inhibited tumor cell growth	↓NF-κB; ↓tyrosine kinase	[238]
Kurarinone	H1688 and H146	6.25, 12.5, and 25 μM	12.5 µM (H1688) and 30.4 µM (H146)	Enhanced cell death	↓EMT; ↓MMP-2	[239]
Luteolin	A549	20–80 μM	40.2 μM	Increased G2/M phase cell cycle arrest and cell death	↑Bax; ↑procaspase-9; ↑caspase-3; ↓NF-κB; ↑JNK	[240]
	A549	25–100 μM	42.8 µM	Decreased cell viability and increased cell death	↑Bax; ↑caspase-3; ↑caspase-9; ↑MEK/ERK; ↓Bcl-2	[241]
	A549 and H460	10–100 μM	40 μM	Inhibited tumor cell growth and increased cell death	↑miR-34a-5p via targeting MDM4	[242,243]
	NCI-H460	20–160 μM	Not reported	Decreased cell viability and increased cell death	↓Bad; ↓Bcl-2; ↑caspase-3; ↓Sirt1	[244]
Moscatilin	H460	1 μM	Not reported	Reduced tumor cell growth	↓ERK; ↓EMT; ↓Akt; ↓Cav-1	[245]
Naringenin	A549	25, 50, 100, 200, and 300 µM	Not reported	Reduced tumor cell growth	↓MMP-2; ↓MMP-9; ↓Akt	[246]
	A549	10, 100, and 200 µM	Not reported	Decreased tumor cell growth and enhanced cell death	↑Caspase-3; ↓MMP-3; ↓MMP-9; ↑p38	[247]
Nobiletin	A549 (adriamycin resistant)	50 µM	Not reported	Enhanced cell death	↑Caspase-3; ↓Akt; ↓GSK-3β; ↓β-catenin; ↓MRP1	[248]
Osthol	A549	25, 50, 100, 150, and 200 μM	Not reported	Increased G2/M phase cell cycle arrest and cell death	↑Bax; ↓cyclin B1; ↓p-Cdc2 ↓Bcl-2; ↓PI3K/Akt	[249]
	A549	40 and 80 µM	Not reported	Inhibited tumor cell growth, migration, and invasion	↓MMP-2; ↓MMP-9	[250,251]
	A549	5–80 μM	Not reported	Inhibited tumor cell growth and metastasis	↓TGF-β-induced EMT; ↓NF-κB; ↓Snail	[252]
Phloretin	A549, Calu-1 H838, and H520	25–75 μg/mL	Not reported	Enhanced cell death	↓Bcl-2; ↓MMP-2; ↓MMP-9; ↑caspase-3; ↑caspase-9	[253]
Phloretin	A549	25, 50, 100, and 200 μM	Not reported	Inhibited tumor cell growth and increased cell death	↑Bax; ↓Bcl-2; ↑caspase-3; ↑caspase-9; ↑ERK; ↑JNK; ↑p38; ↑MAPK; ↑JNK1/2; ↓NF-κB	[254]
Polydatin	A549 and NCI-H1975	50 µM	2.95 µM (A549) and 3.23 µM (NCI-H1975)	Reduced tumor cell growth and increased cell cycle arrest	↑Bak/Bcl-2 ratio	[255]
Pterostilbene	NCI-H460 and SK-MES-1	10–100 μM	Not reported	Decreased cell viability and increased cell death	↑Caspase-3; ↑caspase-7	[256]
Quercetin	A549	0.74–4.40 μM	1.41 μM	Decreased cell growth and increased cell death	↑Bax; ↓Bc1-2	[257]
Resveratrol	A549	20 μM	Not reported	Inhibited tumor cell growth and invasion	↓TGF-β1-induced EMT	[258]
	A549	4–64 μM	8.9 μM	Reduced tumor cell growth and increased cell death	↑Caspase-3	[259]
	H1993	1–10 μM	Not reported	Decreased cell viability and increased cell death	↓Resistance of tyrosine kinase inhibitor	[203]
Salicylic acid	A549	1.5–9.5 mM	6.0 mM	Showed cytotoxicity and suppressed tumor cell growth	Not reported	[260]
Tangeretin derivative	CL1-5, H1299, H226, and A549	2.5 and 5 µM	3.2 µM (CL1-5), 6.7 µM (H1299), 10.2 µM (H226), and 9.8 µM (A549)	Enhanced G2/M phase cell cycle arrest, cell death, mitochondrial dysfunction and reduced tumor cell growth	↑Caspase-3; ↓Bcl-2; ↓survivin; ↓PI3K/Akt/mTOR	[261]
Tatariside B, C, and D	A549	0.001, 0.01, 0.1, 1, 10, and 100 µg/mL	18.31 µg/mL (Tatariside B), 6.44–7.49 μg/mL (Tatariside C), and 2.83 μg/mL (Tatariside D)	Enhanced cytotoxicity, oxidative stress, cell death and reduced tumor cell growth	Not reported	[262]
Sulfur-containing compounds
Allicin	A549 and NCI-H460	10–60 μg/mL	25 µg/mL (A549) and 15 µg/mL (NCI-H460)	Inhibited tumor cell growth	↓Cadherin 2; ↑cadherin 1	[263]
Sulforaphane	H1299, 95-C and 95-D	1–5 μM	9.52 μM (H1299), 9.04 μM (95-C), and 17.35 μM (95-D)	Reduced tumor cell growth and increased S/G2–M phase cell cycle arrest	↓miR-616-5p levels; ↓GSK3β/β-catenin	[264]
	A549 and H1299	0, 5, 10, and 15 mM	Not reported	Inhibited tumor cell growth and enhanced G2/M cell cycle arrest	↑Apoptosis; ↓histone deacetylase	[265]
	A549	2.5 and 5 μM	Not reported	Suppressed tumor cell growth and increased G1/S cell cycle arrest	↓miR-21; ↓CDH1; ↓DNMTs	[266]
Terpenoids
Abietane diterpene	NCI-H460, and A549	10 and 30 µg/mL	14 µM (NCI-H460) and 30 µM (A549)	Enhanced cell death	↑Caspase-3; ↓caspase-9	[267]
β-Sitosterol	A549	50–200 μg/mL	95.19 μg/mL	Enhanced G2/M phase cell cycle arrest	↑Apoptosis	[268]
Cucurbitacin B	A549	10 µM	Not reported	Reduced tumor cell growth and increased cell death	↓CDK2; ↓CDK4; ↓cyclin D; ↓cyclin E; ↓mortalin; ↓hnRNP-K; ↓MMP-2; ↓fibronectin; ↑p53; ↑CARF	[269]
Dihydroartemisinin	PC-14	1 μg/mL	Not reported	Increased cell death	↑p38 MAPK; ↑Ca²⁺	[270]
	LLC cells	5, 10, 20, and 40 µg/mL	26.98 µg/mL	Enhanced G0/G1 phase cell cycle arrest	↑p38 MAPK	[271]
	A549 and H1299	0.23–749.90 µM	80.89 uM	Reduced tumor cell growth	↓Transferrin receptor	[272]
Oridonin	H1975	10 µM	Not reported	Decreased tumor cell metastasis and angiogenesis	↓Mesenchymal transition; ↑proapoptotic activity	[273]
	A549	10, 20, and 30 μM	Not reported	Reduced tumor cell metastasis and angiogenesis	↑Bax; ↑cisplatin-induced apoptosis via AMPK/Akt/mTOR; ↑PARP expression	[274]
Soyasapogenol	H-1299	2–10 µM	6 µM	Reduced tumor cell growth, metastasis and increased cell death	↓CDK2; ↓CDK4; ↓cyclin A; ↓cyclin D1; ↓pATR-Chk1 ↓catenin/vimentin/hnRNPK-mediated EMT	[275]
Thymoquinone	LNM35	1–100 µM	50–78 µM	Suppressed tumor cell growth and increased cell death	↑Caspase-3	[276]
Ursolic acid	A549	11, 22, 44, and 88 µM	Not reported	Decreased cell viability and enhanced autophagy	↑LC3-II/LC3-I ratio; ↑p62; ↑PINK1; ↑Nrf2; ↑ROS; ↓p-Akt/mTOR	[277]
	H1975	0.001–0.1 µM	Not reported	Reduced tumor cell growth and angiogenesis	↓N-cadherin; ↓MMP-2; ↓MMP-9; ↓TGF-β1; ↑E-cadherin	[278]
	A549, H460, H1975, H1299, H520, H82, LLC, and H446	5–40 µM	Not reported	Inhibited tumor cell growth and angiogenesis	↓Bcl-2; ↑cleaved PARP; ↑LC3-II; ↓p-S6K T389; ↓p-Akt	[279]
Withaferin A	A549	10 µM	Not reported	Increased cell death, oxidative stress and decreased cell viability	↑ROS	[280]
Miscellaneous compounds
Cannabidiol	A549 and H460	3 µM	Not reported	Increased cell death	↑ICAM-1	[281,282]
Cannabidiol	A549 and H460	1–10 µM	3.47 µM (A549) and 2.80 µM (H460)	Increased cell death	↑ICAM-1; ↑COX-2; ↑PPAR-γ	[283]
	A549	3 µM	Not reported	Enhanced cell death and reduced tumor cell growth	↑MMP-1	[284]
Cypripedin	H23	50 μM	Not reported	Suppressed tumor cell growth	↓N-cadherin; ↓vimentin; ↓Akt/GSK-3β	[285]
Cypripedin	H460	50 μM	Not reported	Inhibited tumor cell growth	↓Bcl-2	[286]
Daucosterol	A549	50–200 μg/mL	17.46 μg/mL	Reduced tumor cell growth and enhanced G2/M phase cell cycle arrest	↓Bcl-2; ↑Bax; ↑caspase-3	[268]
Emodin	A549 and H1299	20, 40, 60, and 80 μM	Not reported	Enhanced cell death	↑ER stress; ↑TRIB3/NF-κB	[287]
Glossogin	A549	12.5 μg/mL	Not reported	Suppressed tumor cell growth	↑Cyt c; ↑caspase-9; ↑caspase-3; ↑Bak/Bcl-2 ratio	[288]
Ouabain	A549 and H1975	25 nM	Not reported	Inhibited tumor cell growth	↑JNK; ↓Bcl-2	[289]
Physalin A	H292, H358, and H1975	5, 10, and 15 μM	Not reported	Decreased tumor cell growth and enhanced cell death	↓JAK/STAT3	[290]
Rhein	A549	25, 50, and 100 μM	45 μM	Enhanced G0/G1 phase cell cycle arrest and cell death	↑ER stress; ↑p53; ↑p21; ↑Bax; ↓Bcl-2; ↓GADD153; ↓cyt c	[291,292]
	A549	25, 50, and 100 μM	100 μM	Inhibited tumor cell growth	↓Bcl-2; ↓p-PI3K; ↓Akt; ↓mTOR	[293]
	PC-9, H460, and A549	30, 60, and 100 µM	24.59 µM (PC-9), 52.88 µM(H460), and 23.9 µM (A549)	Increased G2/M phase cell cycle arrest and cell death	↓Bcl-2; ↑Bax; ↓STAT3	[294]
Withanone	A549	2.5–10 µM	Not reported	Reduced tumor cell growth and increased cell death	↓CDK2; ↓CDK4; ↓cyclin D; ↓cyclin E ↓mortalin; ↓hnRNP-K; ↓MMP-2; ↓fibronectin; ↑p53; ↑CARF	[269]

Symbols and abbreviations: ↑, increased or upregulated; ↓, decreased or downregulated; AIF, apoptosis-inducing factor; Bax, Bcl-2-associated X protein; Bcl-2, B cell lymphoma-2; CARF, calcium-response factor; CDK, cyclin-dependent kinase; COX, cyclooxygenase; DNMT, DNA methyltransferase; EGFR, epidermal growth factor receptor; EMT, epithelial to mesenchymal transition; ERK, extracellular signal-related kinase; GSH, glutathione; GSK3β, glycogen synthase kinase 3β; HO-1, heme oxygenase-1; ICAM-1, intercellular adhesion molecule-1; IL, interleukin; iNOS, inducible nitric oxide synthase; JAK, Janus kinase; MAPK, mitogen-activated protein kinase; Mcl-1, myeloid cell leukemia-1; MEK, mitogen-activated protein kinase; MLK3, mixed lineage kinase 3; MMP-3, matrix metalloproteinase-3; MRP1, multidrug resistance protein 1; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor-κB; PARP, poly (ADP-ribose) polymerase; PERK, protein kinase RNA-like endoplasmic reticulum kinase; PGE2, prostaglandin E2; PI3K, phosphatidylinositol-3-kinase; PPAR-γ, peroxisome proliferator-activated receptor-γ; ROS, reactive oxygen species; STAT, signal transducer and activator of transcription; TGF-β, transforming growth factor-β; VEGF-A, vascular endothelial growth factor-A.