Panduratin A Inhibits the Growth of A549 Cells through Induction of Apoptosis and Inhibition of NF-KappaB Translocation

Cheah, Shiau‐Chuen; Appleton, David R.; Lee, Sui-Ting; Lam, May-Lynn; Hadi, A. Hamid A.; Mustafa, Mohd Rais

doi:10.3390/molecules16032583

Cited by 58 publications

(53 citation statements)

References 22 publications

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“…It is commonly known that there are two apoptotic pathways, the extrinsic, or the death receptor pathway, and the intrinsic, or the mitochondrial pathway. Previous studies have shown that mitochondria play a critical role in apoptosis, especially in the intrinsic apoptosis pathways (21,22). Mitochondria are the main source of ROS inside the cell, and increases in ROS production can damage the mitochondrial membrane and subsequently lead to the release of pro-apoptotic proteins and cytochrome c, thus activating the apoptotic pathway (23)(24)(25).…”

Section: Discussionmentioning

confidence: 99%

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In vitro antitumor effects of two novel oligostilbenes, cis- and trans-suffruticosol D, isolated from Paeonia suffruticosa seeds

Almosnid

Gao

et al. 2015

International Journal of Oncology

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Abstract. Naturally derived stilbenes have been shown to elicit cytotoxic, anti-steroidal, anti-mutagenic, anti-oxidative, anti-inflammatory, and antitumor bioactivities. Previous phytochemical studies revealed that the seeds of Paeonia suffruticosa are rich in natural stilbenes. In this study the antitumor effects and mechanism of action of the oligostilbene isomers, cis-and trans-suffruticosol D, isolated from the seeds of P. suffruticosa were examined. cis-and transsuffruticosol D exhibited remarkable cytotoxicity against the human cancer cell lines A549 (lung), BT20 (breast), MCF-7 (breast), and U2OS (osteosarcoma), but showed significantly less toxicity to the normal human cell lines HMEC (breast) and HPL1A (lung). We also demonstrated that cis-and transsuffruticosol D exerted their antitumor effects by provoking oxidative stress, stimulating apoptosis, decreasing the mitochondrial membrane potential, inhibiting cell motility, and blocking the NF-κB pathway in human lung cancer cells. In addition, we evaluated their respective bioefficacy and found that trans-suffruticosol D is more potent than cissuffruticosol D. Collectively, our results suggest that cis-and trans-suffruticosol D could be promising chemotherapeutic agents against cancer. IntroductionCurrent cancer medications are costly and often cause serious side effects. The US National Cancer Institute began investigating antitumor plant extracts in the 1960s, and the premise that natural compounds obtained from therapeutic plants could produce anticancer medications has henceforth been of great research interest. Traditional Chinese medicines (TCMs) using dried plants or plant extracts have provided low cost diet and pharmaceutical therapies for thousands of years and experimental and clinical studies have proven that >400 plant species used in TCMs as anticancer herbal medications are significantly effective in the prevention or treatment of various cancers (1-4). However, much work remains to be done to determine the effectiveness of the individual compounds present in the TCMs.Paeonia suffruticosa, or Paeoniaceae, is a widely utilized Chinese medicinal plant within the Paeonia genus. This genus comprises ~35 species that are classified into three groups: Oneapia, Paeonia, and Moutan (5). The Cortex Moutan (root cortex) of Paeonia has been recorded by China's Pharmacopoeia as a significant source of herbal medicine (6). Extracts of Paeonia have been shown to possess cytotoxic, antitumor, anti-inflammatory and anti-oxidative activities (5). Previous photochemical research on Paeonia identified >260 bioactive compounds, including phenols, monoterpenoidglucosides, paeonols, flavonoids, tannins, steroids, triterpenoids and stilbenes (7). A more recent study showed that the seeds of Paeonia contain considerable quantities of stilbenes compared to the other compounds (7,8).Stilbenes are a class of polyphenols widely found in plants that contain a 1.2-diphenylethylene nucleus in their structure (9). Stilbenes have aroused great interest due to their antit...

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Section: Discussionmentioning

confidence: 99%

“…The NF-κB pathway is known to control cell growth and survival, and the transcription factor NF-κB has been found to be permanently activated in various tumors (21). Activation of NF-κB in cancer cells is often associated with drug resistance as both radio-and chemo-therapies induce constitutive activation of the NF-κB pathway (43).…”

Section: Discussionmentioning

confidence: 99%

In vitro antitumor effects of two novel oligostilbenes, cis- and trans-suffruticosol D, isolated from Paeonia suffruticosa seeds

Almosnid

Gao

et al. 2015

International Journal of Oncology

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“…The IC 50 value of this compound was 4.4 μ g/mL, as determined by MTT assay, whereas cell cycle analysis via flow cytometer showed cell cycle arrest at mitotic/M phase. Panduratin A also acted as nuclear factor kappa beta (NF- κ B) inhibitor, as treatment at apoptosis-inducing concentration was found to inhibit translocation of NF- κ B from cytoplasm to nuclei by the activation of tumour necrosis factor alpha (TNF- α ) [65]. …”

Section: Anticancer/antitumourmentioning

confidence: 99%

Boesenbergia rotunda: From Ethnomedicine to Drug Discovery

Eng-Chong

Lee

Chin-Fei

et al. 2012

Evidence-Based Complementary and Alternative Medicine

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Boesenbergia rotunda is a herb from the Boesenbergia genera under the Zingiberaceae family. B. rotunda is widely found in Asian countries where it is commonly used as a food ingredient and in ethnomedicinal preparations. The popularity of its ethnomedicinal usage has drawn the attention of scientists worldwide to further investigate its medicinal properties. Advancement in drug design and discovery research has led to the development of synthetic drugs from B. rotunda metabolites via bioinformatics and medicinal chemistry studies. Furthermore, with the advent of genomics, transcriptomics, proteomics, and metabolomics, new insights on the biosynthetic pathways of B. rotunda metabolites can be elucidated, enabling researchers to predict the potential bioactive compounds responsible for the medicinal properties of the plant. The vast biological activities exhibited by the compounds obtained from B. rotunda warrant further investigation through studies such as drug discovery, polypharmacology, and drug delivery using nanotechnology.

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“…This study was conducted using Cellomics Multiparameter Cytotoxicity 3 Kit as described previously [18–20]. Briefly, cells were treated with ZER-HP β CD inclusion complex at 11.43 μ g mL −1 concentration.…”

Section: Methodsmentioning

confidence: 99%

Inclusion Complex of Zerumbone with Hydroxypropyl-β-Cyclodextrin Induces Apoptosis in Liver Hepatocellular HepG2 Cells via Caspase 8/BID Cleavage Switch and Modulating Bcl2/Bax Ratio

Nadzri

Abdul

Sukari

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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Zerumbone (ZER) isolated from Zingiber zerumbet was previously encapsulated with hydroxypropyl-β-cyclodextrin (HPβCD) to enhance ZER's solubility in water, thus making it highly tolerable in the human body. The anticancer effects of this new ZER-HPβCD inclusion complex via apoptosis cell death were assessed in this study for the first time in liver hepatocellular cells, HepG2. Apoptosis was ascertained by morphological study, nuclear stain, and sub-G1 cell population accumulation with G2/M arrest. Further investigations showed the release of cytochrome c and loss of mitochondrial membrane potential, proving mitochondrial dysfunction upon the ZER-HPβCD treatment as well as modulating proapoptotic and anti-apototic Bcl-2 family members. A significant increase in caspase 3/7, caspase 9, and caspase 8 was detected with the depletion of BID cleaved by caspase 8. Collectively, these results prove that a highly soluble inclusion complex of ZER-HPβCD could be a promising anticancer agent for the treatment of hepatocellular carcinoma in humans.

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Panduratin A Inhibits the Growth of A549 Cells through Induction of Apoptosis and Inhibition of NF-KappaB Translocation

Cited by 58 publications

References 22 publications

In vitro antitumor effects of two novel oligostilbenes, cis- and trans-suffruticosol D, isolated from Paeonia suffruticosa seeds

In vitro antitumor effects of two novel oligostilbenes, cis- and trans-suffruticosol D, isolated from Paeonia suffruticosa seeds

Boesenbergia rotunda: From Ethnomedicine to Drug Discovery

Inclusion Complex of Zerumbone with Hydroxypropyl-β-Cyclodextrin Induces Apoptosis in Liver Hepatocellular HepG2 Cells via Caspase 8/BID Cleavage Switch and Modulating Bcl2/Bax Ratio

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