Plant-Derived Anticancer Agents: Lessons from the Pharmacology of Geniposide and Its Aglycone, Genipin

Abstract

For centuries, plants have been exploited by mankind as sources of numerous cancer chemotherapeutic agents. Good examples of anticancer compounds of clinical significance today include the taxanes (e.g., taxol), vincristine, vinblastine, and the podophyllotoxin analogues that all trace their origin to higher plants. While all these drugs, along with the various other available therapeutic options, brought some relief in cancer management, a real breakthrough or cure has not yet been achieved. This critical review is a reflection on the lessons learnt from decades of research on the iridoid glycoside geniposide and its aglycone, genipin, which are currently used as gold standard reference compounds in cancer studies. Their effects on tumour development (carcinogenesis), cancer cell survival, and death, with particular emphasis on their mechanisms of actions, are discussed. Particular attention is also given to mechanisms related to the dual pro-oxidant and antioxidant effects of these compounds, the mitochondrial mechanism of cancer cell killing through reactive oxygen species (ROS), including that generated through the uncoupling protein-2 (UCP-2), the inflammatory mechanism, and cell cycle regulation. The implications of various studies for the evaluation of glycosidic and aglycone forms of natural products in vitro and in vivo through pharmacokinetic scrutiny are also addressed.

miR‑21/PTEN pathway mediates the cardioprotection of geniposide against oxidized low‑density�lipoprotein‑induced endothelial injury via suppressing oxidative stress and inflammatory response

“…In addition, studies have demonstrated the roles of the miR-21/PTEN pathway in tumor growth, migration and invasion (44,45). combined with previous studies regarding the protection of geniposide against tumor (15,46), miR-21/PTEN pathway may contribute to the antitumor effect of geniposide.…”

“…Geniposide, a major compound extracted from the gardenia fruit, is a type of traditional chinese medicine for the treatment of inflammation, brain disorders and hepatic disease (11). Geniposide exhibits a broad spectrum of pharmacological actions involving anti-apoptosis (12), anti-inflammatory injury (13), anti-oxidative stress (14), anti-cancer (15) and anti-angiogenesis effects (16). Previous in vitro and in vivo studies have focused on the potential cardioprotective effects of geniposide, particularly in atherosclerosis (17)(18)(19).…”

Retracted: Geniposide exhibits anticancer activity to medulloblastoma cells by downregulating microRNA‐373

“…[ 11,12 ] Geniposide (CAS number: 24512‐63‐8; Figure 1) is the main active ingredient separated and purified from the fruit of Gardenia jasminoides Ellis. [ 13 ] Earlier research reported that geniposide possessed beneficial activities, [ 14 ] such as anti‐inflammation, [ 15 ] antidiabetes, [ 16 ] antiangiogenesis, [ 17 ] antitumor, [ 18 ] and neuroprotection. [ 19 ] For antitumor activity, Qian et al [ 20 ] indicated that geniposide could inhibit cell proliferation and induce cell apoptosis of human oral squamous carcinoma HSC‐3 cells.…”

The Chemistry, Pharmacology and Therapeutic Potential of the Edible Mushroom Dictyophora indusiata (Vent ex. Pers.) Fischer (Synn. Phallus indusiatus)

“…A further possible mechanism for the induction of apoptosis was mitochondrial dysfunction and ROS overproduction induced by the zinc chelate of DP1. Induction of ROS overproduction through the mitochondrial respiratory pathways leading to caspases activation and apoptosis appears to be consistent to the anticancer activity of many natural products [58]. The same group also prepared a monodispersed selenium nanoparticle of DP1 that induce apoptosis in HepG2 cells through exactly the same above-mentioned mechanism [40].…”