Aloe-emodin suppresses prostate cancer by targeting the mTOR complex 2

Abstract

Phosphatidylinositol 3-kinase (PI3-K) amplification and phosphatase and tensin homolog (PTEN) deletion-caused Akt activation contribute to the development of prostate cancer. Mammalian target of rapamycin complex 2 (mTORC2) is a kinase complex comprised of mTOR, Rictor, mSin1, mLST8/GβL and PRR5 and functions in the phosphorylation of Akt at Ser473. Herein, we report that mTORC2 plays an important role in PC3 androgen refractory prostate cell proliferation and anchorage-independent growth. Aloe-emodin, a natural compound found in aloe, inhibited both proliferation and anchorage-independent growth of PC3 cells. Protein content analysis suggested that activation of the downstream substrates of mTORC2, Akt and PKCα, was inhibited by aloe-emodin treatment. Pull-down assay and in vitro kinase assay results indicated that aloe-emodin could bind with mTORC2 in cells and inhibit its kinase activity. Aloe-emodin also exhibited tumor suppression effects in vivo in an athymic nude mouse model. Collectively, our data suggest that mTORC2 plays an important role in prostate cancer development and aloe-emodin suppresses prostate cancer progression by targeting mTORC2.

Aloe-emodin suppresses esophageal cancer cell TE1 proliferation by inhibiting AKT and ERK phosphorylation

“…Aloe-emodin induced apoptosis, autophagy and differentiation of glioma cells by inhibiting the action of ERK (54). In the current study, aloe-emodin at low doses inhibited AKT and ERK phosphorylation, which is consistent with a previous study by the present authors on prostate cancer cells (PC3) (36). However, PTEN loss caused strong activation of AKT, which, in turn, attenuated the phospho-ERK signal.…”

“…Previous studies have demonstrated that aloe-emodin induces cell death through S-phase arrest in human tongue squamous cancer SCC-4 cells (38). A previous study by the present authors also indicated that mTORC2 is a target of aloe-emodin, and aloe-emodin can strongly inhibit the AKT activation caused by PTEN loss (36). Aloe-emodin is a natural compound from aloe or Rheum palmatum (39,40).…”

“…Aloe-emodin has anti-cancer activity in neuroectodermal tumors (31), nasopharyngeal carcinoma (32), lung squamous cell carcinoma (33), hepatoma cells (34), gastric cancer (35) and prostate cancer (36). Aloe-emodin induces apoptotic cell death by oxidative stress and sustained c-Jun N-terminal kinase (JNK) activation (37).…”

Aloe Vera and Cancer

“…It is claimed to be effective in a variety of applications, but it is potential effect on cancer has been of particular [24] Laboratory Breast cancer Suppressed the proliferation Suboj P et al [25] Laboratory Colon cancer Induced apoptosis Lee HZ et al [26] Laboratory Lung carcinoma Inhibited cell growth in cell lines Chen HC et al [27] Laboratory Promyelocytic leukemia Inhibited cell growth in cell lines Pecere T et al [28] Laboratory Neuroectodermal tumors Inhibited cell growth in cell lines Pan Q et al [29] Laboratory Colorektal cancer Inhibited the angiogenesis through VEGF suppression Yonehara A et al [30] Laboratory Neuroblastoma Suppressing the cyclin D2 transcription level Liu K et al [31] Laboratory Prostate cancer Inhibit cancer cell proliferation by acting through mammalian target of rapamycin complex 2 Heggie S et al [13] Clinical Breast cancer No significant benefit in skin problems caused by radiotherapy Williams MS et al [14] Clinical -No significant benefit in skin problems caused by radiotherapy George J et al [16] Clinical Head and neck cancer Delay the start time of radiotherapy induced skin lesions and reduce their intensity Lissoni P et al [20] Clinical Metastatic cancers Tumor regression Su CK et al [36] Clinical Head and neck cancer No contribution in terms of reducing the symptoms and increasing quality of life interest in recent years. The most advocated benefit of Aloe vera for a cancer patient is its alleged ability to prevent and treat skin lesions caused by radiotherapy.…”

“…[30] In a study on prostate cancer cell cultures (PC3), Aloe emodin was found to inhibit prostate cancer cell proliferation by acting through mammalian target of rapamycin complex 2 (mTORC2) ( Table 1). [31] …”