TABLE 2.
Summary of recent preclinical and clinical trials of plant-based alkaloids on cancer treatment.
| Alkaloid type | Preclinical research | Clinical trial | Reference | |
|---|---|---|---|---|
| In vitro studies | In vivo studies | |||
| Nitidine chloride | Liver cancer: Huh7 (IC50 = 5.006 μM); SMMC7721 (IC50 = 1.332 μM) | Liver cancer: Tumor volume decreased in BALB/c nude mice injected with SMMC7721 | Not applicable | Xiong et al. (2019) |
| Sophoridine | Lung Cancer: H460 ((IC50 = 73.49 μg/ml/24 h); (IC50 = 53.52 μg/ml/48 h)); Lewis ((IC50 = 64.95 μg/ml/24 h); (IC50 = 40.49 μg/ml/48 h)) | Lung cancer: 15 or 25 mg/kg suppressed the tumor growth and upregulated the expression of CD86/F4/80 in tumor tissues in the Lewis-bearing mice model | Not applicable | Peng et al. (2020) |
| Gastric cancer: SGC7901 (IC50 = 3.52 μM/12 h); AGS (IC50 = 3.91 μM/12 h); GES-1 (IC50 = 51.40 μM/12 h) | Zhao et al. (2021) | |||
| Palmatine | Colon cancer: HT-29 (IC50 = 68.3 µM); SW-480 (IC50 = 72.6 µM) | Colon cancer: Gavage once a day with 33.75, 67.5, and 135 mg/kg inhibits the growth of HCT-116 xenograft tumors; −10 to 20 mg/kg/day decreased tumor numbers in the small intestine and colon in ApcMin/+ mice | Not applicable | Johnson-Ajinwo et al. (2019) |
| Ovarian cancer: IC50 values ranging from 5.5 to 7.9 µM | Tuzimski et al. (2021) | |||
| Melanoma: A375 (IC50 > 200 μg/ml); G361 (IC50 = 119.98 μg/ml); SK-MEL-3 (IC50 = 88.04 μg/ml) | Hambright et al. (2015) | |||
| Prostate cancer: DU145 (IC50 = 10 μg/ml) | Liu et al. (2020a) | |||
| Gastric cancer: MKN-45 (IC50 = 332.43 µM) | Ma et al. (2016) | |||
| Yu et al. (2020) | ||||
| Aleutianamine | Pancreatic cancer: PANC-1 (IC50 = 25 nM) | Not applicable | Not applicable | Zou et al. (2019) |
| Colon cancer: HCT-116 (IC50 = 1 μM) | ||||
| Nuciferine | Lung cancer: A549/T (IC50 = 105.1 μM); A549 (IC50 = 129.4 μM) | Lung cancer: Moderate tumor growth inhibition in the A549/T xenograft model in BALB/c-nu/nu mice treated with 7.5 mg/kg/ip/3 days for 27 days | Not applicable | Li et al. (2019) |
| Glioblastoma: U87MG (IC50 = 72.3 μM); U251 (IC50 = 59.9 μM) | Glioblastoma: Inhibition of tumor volume growth in glioblastoma xenograft BALB/c nude mouse models | Liu et al. (2020b) | ||
| Breast cancer: 60 μM reduced cell viability to 40% in MDA-MB-231 and 20% in MCF-7 cells | Kang et al. (2017) | |||
| Liver cancer: 100 μM reduced cell viability to 60% in HepG2 and Huh7; and 40% in HCClM3 | ||||
| Cervical carcinoma: 100 μM reduced cell viability of HeLa to 45% | ||||
| Colon carcinoma: HCT-8/T (IC50 = 104.79 μM); HCT-8 (IC50 = 164.16 μM) | ||||
| Lung cancer: A549/T (IC50 = 105.1 μM); A549 (IC50 = 129.4 μM) (Z. Li et al., 2019) | ||||
| Methylxanthines | Breast cancer: MDA-MB-231 (IC50 > 100 μM, Theophyline) | Breast cancer: Not applicable | Breast cancer: Study phase not applicable a ; (NCT03482401) | Hashemi-Niasari et al. (2018) |
| Gastric cancer: MGC-803 (IC50 = 4 mM, Caffeine); MGC-803 (IC50 = 8 mM, Theophylline) | Gastric cancer: BALB/c nude mice injected intraperitoneally with caffeine (4 mM) or theophylline (8 mM) results in reducing tumor size | Liu et al. (2019a) | ||
| Oral epidermoid carcinoma: KB (IC50 = 2.5 mM/48 h) | Ávila-Gálvez et al. (2019) | |||
| Lung cancer: H1355 (IC50 = 2.5 mM/48) | Caraglia et al. (2002) | |||
| Melanoma: GLL-1 (IC50 = 2.5 mM/48) | Beklen et al. (2021) | |||
| Colon carcinoma: HCT-116 (IC50 = 500 μM/72 h) | ||||
| Berberine | Colon cancer: SW620 (IC50 = 54.41 μM/48 h); LoVo (IC50 = 78.66 μM/48 h) | Colon cancer: Dose of 10 mg/kg/qd/ip/for 2 weeks reduces tumor volume in Balb/c mice | Colorectal adenoma: Phase II, Phase III; NCT02226185 | Zhao et al. (2017) |
| Breast cancer: BT549 (IC50 = 16.575–1.219 mg/ml); MDA-MB-231 (IC50 = 18.525–6.139 mg/ml) | Breast cancer: Oral dose (100 mg/kg)/3 days inhibited tumor growth and increased caspase-9 levels in MDA-MB-231 in the BALB/c mouse-xenograft model; −0.1% in the drinking water/day during 6.6 w promoted the antitumoral activity in female Balb/c; −50 mg/kg/po decreased the tumor size in rats | Kim et al. (2018) | ||
| Glioblastoma: U87 (IC50 = 42 μM); U251 (IC50 = 32 μM) | Glioblastoma: 50 mg/kg berberine reduced tumor weight and improved the survival rate of mice in the ectopic tumor xenograft mouse model and inhibits angiogenesis in glioblastoma xenografts | Karnam et al. (2017) | ||
| Ovarian cancer: OVCAR3 (IC50 = 99 μM, 24 h) | Nasopharyngeal carcinoma: 10 mg/kg/ip/qd for 3 weeks decreases the tumor volume in female NOD/SCID mice | Liu et al. (2019b) | ||
| Gastric cancer: Antitumoral activity at 50 mg/po/qd during 4 weeks in Balb/c mice | Jin et al. (2018) | |||
| Neuroepithelial tumor: Treatment with 10 mg/kg/qd/ ip during 1 week showed antitumor effect in Balb/c mice | Ruan et al. (2017) | |||
| Endometrial carcinoma: Antitumoral activity at 50 mg/kg/po during 4 weeks in Balb/c mice | Wang et al. (2017a) | |||
| Wang et al. (2016) | ||||
| Sun et al. (2018b) | ||||
| Wang and Zhang (2018) | ||||
| Liu et al. (2015) | ||||
| Homoharringtonine | Breast cancer: MDA-MB-157 (IC50 = 15.7 ng/ml, 24 h); MDA-MB-468 (IC50 = 19.9 ng/ml, 24 h); CAL-51 (IC50 = 23.1 μg/ml, 24 h); MDA-MB-231 (IC50 = 80.5 ng/ml, 24 h); MDA-MD-231 (IC50 = 0.31 μg/ml); HCC 1937 (IC50 = 0.32 μg/ml); T47D (IC50 = 1.27 μg/ml); MCF7 (IC50 = 0.45 μg/ml) | Breast cancer: 1 mg/kg given subcutaneously, twice daily, over 7 days suppresses growth of MDA-MB-231 and MDA-MB-468 in Swiss nu/nu female mice; −50 μg/kg/day injected intraperitoneally for 10 days inhibited breast cancer cell growth in female and male BLAB/c nude mice | Hematologic malignancies solid tumors: Phase I; NCT01844869 | Wang et al. (2021) |
| Liver cancer: HepG2 (IC50 = 0.025 μM); Bel-7402 (IC50 = 0.251 μM); Hep3B (IC50 = 0.291 μM); Bel-7404 (IC50 = 0.694 μM); SMMC-7721 (IC50 = 1.220 μM) | Liver cancer: 0.1 mg/kg, 0.2 mg/kg, and 0.4 mg/kg administered orally decreased tumor growth and the inhibitory rate of 20, 50, and 55% in mal nude mice, respectively | Leukemia: Phase III; NCT00004933 | Yakhni et al. (2019) | |
| Acute myeloid leukemia: MV4-11 (IC50 = 0.15 nM/24 h; 5.32 nm/48 h); MOLM13 (IC50 = 6.06 nM/24 h; 1.54 nM/48 h); CCL-AML2 (IC50 = 65 nM/24 h; 4.67 nM/48 h); CCL-AML3 (IC50 = 23.94 nM/24 h; 4.85 nM/48 h) | Acute myeloid leukemia: 1.0 mg/kg/day by oral administration for 2 weeks suppressed AML progression and cell growth in the xenograft female NOD/SCID mice model | Acute myelogenous leukemia: Phase II; NCT01873495 | Zhu et al. (2020) | |
| Hematologic tumors: Phase I; NCT00675350 | Shi et al. (2021) | |||
| Leukemia: NCT02159872; Phase II | ||||
| Chronic myeloid leukemia: Phase I/II; NCT02078960 | ||||
IC50: Half maximal inhibitory concentration.
a
Study phase not applicable describes trials without Food and Drug Administration (FDA)–defined phases.
NCT: Clinical trial umber.