Caspases are key mediators of apoptosis. Caspase-8 mediates extrinsic, and caspase-9 initiates the intrinsic pathway of apoptosis[3]. Ginsenoside Rh2 (G-Rh2), isolated from the root of Ginseng, is an activator of caspase-8 and caspase-9 and induces cancer cell apoptosis in a multi-path manner. The cell viability of the human tumor cell lines HeLa, SK-HEP-1, SW480, and PC-3 was remarkably inhibited by G-Rh2, with IC50s of 2.52, 3.15, 4.06 and 7.85 μg/mL, respectively. G-Rh2 might have the unique ability to simultaneously and independently activate both caspase-8 and caspase-9 in HeLa cells. In HeLa cells treated with 7.5 μg/mL G-Rh2 for 4 h, Fas (key factor for caspase-8 activation) and TNF-R1 were remarkably up-regulated by G-Rh2 in a time-dependent manner. Furthermore, significant increases in Fas expression and caspase-8 activity following G-Rh2 treatment coincided with an increase in p53 expression in p53-non-mutated HeLa and SK-HEP-1 cells indicating that G-Rh2 may act as a stabilizer for p53[4]. In male C57BL6 mice, the tumor sizes in the G-L group and G-H group (G-L and G-H refer to a low or high dose of G-Rh2 injection) were reduced compared with the tumor group. Moreover, the G-Rh2 treated mice survived longer than the untreated ones in a dose-dependent manner[5].
Ginsenoside Rh2/人参皂苷Rh2 细胞实验
Cell Line
Concentration
Treated Time
Description
References
A549
10 μmol/L
24 hours
To evaluate the anti-cancer effect of Ginsenoside Rh2 on A549 cells. Results showed that Eve-Rh2 significantly triggered cell death within 24 h with cell inhibitory rates of 55.44±4.73%.
Acta Pharm Sin B. 2022 Mar;12(3):1240-1253
HCC827
10 μmol/L
24 hours
To evaluate the anti-cancer effect of Ginsenoside Rh2 on HCC827 cells. Results showed that Eve-Rh2 significantly triggered cell death within 24 h with cell inhibitory rates of 54.80±12.83%.
Acta Pharm Sin B. 2022 Mar;12(3):1240-1253
NCI-H1975
10 μmol/L
24 hours
To evaluate the anti-cancer effect of Ginsenoside Rh2 on NCI-H1975 cells. Results showed that Eve-Rh2 significantly triggered cell death within 24 h with cell inhibitory rates of 78.24±8.74%.
Acta Pharm Sin B. 2022 Mar;12(3):1240-1253
PC-3 cells
7.5 μg/mL
1-8 hours
To investigate the apoptosis-inducing effect of G-Rh2 on p53-mutated PC-3 cells, results showed that G-Rh2 did not affect Fas expression and caspase-8 activity.
Protein Cell. 2014 Mar;5(3):224-34
SW480 cells
7.5 μg/mL
1-8 hours
To investigate the apoptosis-inducing effect of G-Rh2 on p53-mutated SW480 cells, results showed that G-Rh2 activated caspase-9 via the mitochondrial pathway but did not affect Fas expression and caspase-8 activity.
Protein Cell. 2014 Mar;5(3):224-34
SK-HEP-1 cells
7.5 μg/mL
1-8 hours
To investigate the apoptosis-inducing effect of G-Rh2 on SK-HEP-1 cells, results showed that G-Rh2 activated caspase-8 via p53-dependent Fas upregulation.
Protein Cell. 2014 Mar;5(3):224-34
HeLa cells
7.5 μg/mL
1-8 hours
To investigate the mechanism of G-Rh2-induced apoptosis, results showed that G-Rh2 significantly upregulated Fas and TNFR1 expression and activated caspase-8 via p53-dependent Fas upregulation.
Protein Cell. 2014 Mar;5(3):224-34
MCF-7 cells
10 μM
72 hours
Rh2 pretreatment mildly downregulated P-gp expression by reactivating the pentose phosphate pathway and rebalancing redox status, significantly increasing the growth inhibition effect and accumulation profile of adriamycin (ADR) throughout the multicellular tumor spheroid (MCTS) and improving drug penetration.
Redox Biol. 2020 May;32:101452
SW480 cells
30-40 μM
48 hours
To evaluate the cytotoxic effect of Rh2 on SW480 cells, results showed that Rh2 significantly induced cell death.
Cancer Lett. 2011 Feb 28;301(2):185-92
HCT116 cells
35 μM
48 hours
To evaluate the cytotoxic effect of Rh2 on HCT116 cells, results showed that Rh2 significantly induced cell death.
Cancer Lett. 2011 Feb 28;301(2):185-92
MCA205 cells (mouse fibrosarcoma cells)
10 μM
16 hours
To evaluate the effect of G-Rh2 on autophagy and ER stress, results showed that G-Rh2 enhanced autophagy and induced ER stress.
Clin Transl Med. 2023 Feb;13(2):e1109
U2OS cells (human bone osteosarcoma epithelial cells)
1, 5, 10 μM
16 hours
To evaluate the effect of G-Rh2 on autophagy marker LC3-II levels, results showed that G-Rh2 increased LC3-II levels.
Clin Transl Med. 2023 Feb;13(2):e1109
Ginsenoside Rh2/人参皂苷Rh2 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
BALB/c nude mice
MCF-7 subcutaneous tumor model
Oral
50 mg/kg
Once daily for 6 consecutive days
Rh2 pretreatment and withdrawal downregulated P-gp expression by reactivating the pentose phosphate pathway and rebalancing redox status, significantly enhancing the penetration and antitumor effect of adriamycin in tumor tissues.
Redox Biol. 2020 May;32:101452
BALB/c nude mice
Lung cancer xenograft model
Intragastric administration
5 mg/kg/day
Once daily for 28 days
To evaluate the anti-cancer effect of Ginsenoside Rh2 in vivo on lung cancer xenograft models. Results showed that Eve-Rh2 significantly suppressed tumor growth, and Rh2 alleviated the hepatic fat accumulation caused by Eve.
Acta Pharm Sin B. 2022 Mar;12(3):1240-1253
BALB/c mice
4T1 breast carcinoma xenograft model
Intravenous injection
10 mg/kg
Every other day for 21 days
To evaluate the anti-tumor effect of PTX-Rh2-lipo, results showed that PTX-Rh2-lipo significantly suppressed tumor growth and remodeled the tumor microenvironment.
Nanomicro Lett. 2020 Jun 16;12(1):129
BALB/C mice
Endometriosis (EMS) model
Intraperitoneal injection
15 mg/kg, 30 mg/kg, 45 mg/kg
Injected on day 4 and day 10, samples collected on day 14
To evaluate the effect of PPD on ectopic lesions in a mouse EMS model, results showed that PPD significantly reduced the number and weight of ectopic lesions and downregulated ERα expression while upregulating PRα expression.
Cell Death Dis. 2018 May 1;9(5):574
C57BL/6 mice
Lung cancer xenograft model
Intraperitoneal injection
10 and 20 mg/kg/day
Continuously for 21 days
Inhibited tumor growth and metastasis with no significant toxicity
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