Gambogic acid sensitizes breast cancer cells to TRAIL-induced apoptosis by promoting the crosstalk of extrinsic and intrinsic apoptotic signalings

Wang, Shengpeng; Xu, Yingqi; Li, Chenyang; Tao, Hongxun; Wang, Anqi; Sun, Chenyu; Zhong, Zhangfeng; Wu, Xu; Wang, Ying

doi:10.1016/j.fct.2018.02.037

Cited by 17 publications

(13 citation statements)

References 35 publications

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“…Many studies have reported the anti-cancer effects of GA in human breast cancer [647][648][649][650]. GA at low concentrations (0.3-1.2 μM) can inhibit cell invasion without affecting cell viability, while high concentrations of GA (3 and 6 μM) can induce apoptosis via ROS accumulation and mitochondrial apoptotic pathway in human breast cancer MDA-MB-231 cells [651].…”

Section: Gambogic Acid (Ga)mentioning

confidence: 99%

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

et al. 2019

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Numerous natural products originated from Chinese herbal medicine exhibit anti-cancer activities, including antiproliferative, pro-apoptotic, anti-metastatic, anti-angiogenic effects, as well as regulate autophagy, reverse multidrug resistance, balance immunity, and enhance chemotherapy in vitro and in vivo. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2011) on the key compounds with anti-cancer effects derived from Chinese herbal medicine (curcumin, epigallocatechin gallate, berberine, artemisinin, ginsenoside Rg3, ursolic acid, silibinin, emodin, triptolide, cucurbitacin B, tanshinone I, oridonin, shikonin, gambogic acid, artesunate, wogonin, β-elemene, and cepharanthine) in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we focused on their recently discovered and/or investigated pharmacological effects, novel mechanism of action, relevant clinical studies, and their innovative applications in combined therapy and immunomodulation. In addition, the present review has extended to describe other promising compounds including dihydroartemisinin, ginsenoside Rh2, compound K, cucurbitacins D, E, I, tanshinone IIA and cryptotanshinone in view of their potentials in cancer therapy. Up to now, the evidence about the immunomodulatory effects and clinical trials of natural anti-cancer compounds from Chinese herbal medicine is very limited, and further research is needed to monitor their immunoregulatory effects and explore their mechanisms of action as modulators of immune checkpoints.

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Section: Gambogic Acid (Ga)mentioning

confidence: 99%

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

et al. 2019

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“…In breast cancer cells, gambogic acid increased sensitivity of TRAIL and increased TRAIL-induced apoptosis in cancer cells. Wang et al (2018) discovered that GA with TRAIL cooperation decreased anti-apoptotic proteins level and activated Bid (BH3 interacting-domain death agonist) which promoted cross talk between extrinsic and intrinsic apoptotic signaling, instead of enhancing the TRAIL DR4 and DR5 receptors (Wang et al, 2018b). Different researchers and investigators determined that encapsulation of GA with polyethylenimine-poly (d,l-lactide-coglycolide) caused momentous augmentation in apoptotic cell death in an in vitro study on triplenegative breast cancer, and in vivo suppression of TNBC tumor growth (Wang et al, 2017;.…”

Section: Breast Cancermentioning

confidence: 99%

“…Inhibited proliferation and induced apoptotic cell death (Wang et al,2018a;Sang et al, 2018). Increased the sensitivity of breast cancer cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) Enhanced TRAIL-induced apoptosis (Wang et al, 2018b).…”

Section: Mechanisms References Breast Cancermentioning

confidence: 99%

Gambogic Acid as Anticancer Agent: A Review

Gilani¹,

Imran²,

Haq³

et al. 2020

Preprint

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Gambogic acid, a common traditional Chinese medicine and widely distributed throughout South China, Vietnam, Cambodia, and Thailand. It is prenylated xanthone which is the significant bioactive compound of gamboge. Gambogic acid is known as a strong apoptotic inducer in cancer cells. It has been found as strong anticancer agent against various types of cancer cells lines such as breast cancer, pancreatic, and cervical cancer. It induces apoptosis, down regulates the anti-apoptotic proteins (survivin and BCL2,) and down regulates the activities of P-glycoprotein in drug sensitive human breast MCF-7 and drug-resistant MCF-7/ADR cells. Similarly, it also exerts alteration in P13K, AKT, p21, MMP-2 &-9, and phosphorylated-AKT expressions. The current review highlights the anticancer and chemo-preventive perspectives of gambogic acid and its mechanistic role against human and animal cancers.

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“…It also triggers the intrinsic caspase-dependent signaling pathway in neuroblastoma cells (12). In non-TNBC breast cancer, GA induces apoptosis by increasing reactive oxygen species (13); it also increases the sensitivity of breast cancer to TRAIL (TNFrelated apoptosis-inducing ligand)-induced apoptosis by promoting the crosstalk between extrinsic and intrinsic apoptotic signaling pathways (14). Recently, a study also showed that GA increases sensitivity to paclitaxel in drug −resistant TNBC via the sonic hedgehog signaling pathway (15).…”

Section: Introductionmentioning

confidence: 99%

Targeted Chinese Medicine Delivery by A New Family of Biodegradable Pseudo-Protein Nanoparticles for Treating Triple-Negative Breast Cancer: In Vitro and In Vivo Study

Kwan

Gong

et al. 2021

Front. Oncol.

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Triple negative breast cancer (TNBC) has the worst overall survival among all breast cancer subtypes; 80% of TNBC harbors TP53 mutation. Gambogic acid (GA) is an herbal compound isolated from the dry brownish gamboge resin of Garcinia hanburyi. A new family of biodegradable polymer, the folate (FA)-conjugated arginine-based poly(ester urea urethane)s nanoparticles (FA-Arg-PEUU NP), was developed as nano-carrier for GA. Its anti-TNBC effects and the underlying mechanism of action were examined. The average diameters of FA-Arg-PEUU NP and GA-loaded FA-Arg-PEUU NP (NP-GA) in water are around 165 and 220nm, respectively. Rhodamine-tagged FA-Arg-PEUU NP shows that the conjugation of FA onto Arg-PEUU NPs facilitates the internalization of FA-Arg-PEUU-NP into TNBC. Compared to free-GA at the same GA concentrations, NP-GA exhibits higher cytotoxicity in both TP53-mutated and non-TP53 expressed TNBC cells by increasing intrinsic and extrinsic apoptosis. In HCC1806-bearing xenograft mouse model, the targeted delivery of GA by the FA-Arg-PEUU-NP nano-carriers to the tumor sites results in a more potent anti-TNBC effect and lower toxicity towards normal tissues and organs when compared to free GA. Furthermore, NP-GA also reduces the tumor-associated macrophage (TAM) M1/M2 ratio, suggesting that the use of Arg-based nanoparticles as carriers for GA not only makes the surface of the nanoparticles positively charged, but also confers on to the nanoparticles an ability to modulate TAM polarization. Our data clearly demonstrate that NP-GA exhibits potent anti-TNBC effects with reduced off-target toxicity, which represents novel alternative targeted therapeutics for TNBC treatment.

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Gambogic acid sensitizes breast cancer cells to TRAIL-induced apoptosis by promoting the crosstalk of extrinsic and intrinsic apoptotic signalings

Cited by 17 publications

References 35 publications

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

Gambogic Acid as Anticancer Agent: A Review

Targeted Chinese Medicine Delivery by A New Family of Biodegradable Pseudo-Protein Nanoparticles for Treating Triple-Negative Breast Cancer: In Vitro and In Vivo Study

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