TABLE 2.

Potential Anticancer action of capsaicin and its analogs.

Agent	Effect	Pathway/Mediators	References
I. Capsaicin
↑ Antioxidant defense	↑ PI3K/Nrf2/HO-1 pathway	Clark and Lee (2016), Cho et al. (2017), Friedman et al. (2018)
↑ Antioxidant defense	↑GST, ↑QR and ↑HO-1
↓ Lipid peroxidation	↑SOD, ↑CAT, ↑GPx, ↑GR, ↑ G6PD
↑ Chemotherapeutic efficacy	↓P-gp
↓ Inflammation	↓Substance-P, ↓IL-1β, ↓IL-6, ↓TNFα, ↓Cox-2, ↓NF-κB
↓Activation of carcinogens	↓CYP1A1, ↓CYP1A2, ↓CYP3A4/5, ↓CYP2B6, ↓CYP2C19, ↓CYP2D6 and ↓CYP2E1
II. Natural Capsaicin Analogues
Capsiate & Dihydrocapsiate	↑ Apoptosis	↑ROS, ↑NF-κB ↓ ΔΨm	Friedman et al. (2018)
	↓ Angiogenesis	↓ Src Kinase, ↓ p125, ↓ p125, ↓ VE-Cadherin
Evodiamine and
Rutaecarpine	↑Apoptosis	↑p53 and ↑p21 cells
	↑Autophagy	↑ ROS, ↑NO, ↑Bax,↑Ca2+, ↓ Bcl-2, ↓JNK
	↓Angiogenesis	↓ MAPK and ↓ERK
	↓Metastasis	↓MMP2,3, ↓JAK/STAT, ↓PGI
Resiniferatoxin	↑Cell Cycle Arrest	↓ΔΨm, ↑PKC, ↑p21, ↓CCND1
	↑Apoptosis	↓CoQ, ↓Mitochondrial Respiration
DihydroCapsaicin	↑Apoptosis	↓ΔΨm, ↑Cyt-c, ↑Cytosolic Ca2+, ↑Cas-3 and 9
	↑Autophagy	↑Catalase
II. Capsaicin synergistic action with other compounds
Combination	Mechanism	Type of cancer	Clark and Lee (2016)
Capsaicin + Resveratrol	↑ Apoptosis - p53-dependent NO elevation and enhanced caspase-3 activity	Colon Cancer
Capsaicin + Pirarubicin	TRPV1 activation and inhibition of nuclear localization of PCNA	Bladder Cancer
Capsaicin + Genistein	↑AMPK, ↓Cox-2	Breast Cancer
Capsaicin +3,3′-diindolylmethane	Modulating the transcriptional activity of NF-κB, ↑OR↓ target genes downstream of NF-κB and p53	Colorectal Cancer
Capsaicin + Brassinin	↓ MMP-2 and -9 expression and enzymatic activities	Prostate Cancer
Capsaicin+
5-FU/cisplatin/docetaxel, doxorubicin	↑phospho- MLKL, phospho- RIP3 and
↑ necroptosis	HSC-3 and SAS oral cancer cell lines	Huang et al. (2021)

Abbreviations: ΔΨm- Mitochondrial membrane potential, Cytochrome-c–Cyt-c.