Lung Cancer Stem Cells and Cancer Stem Cell-targeting Natural Compounds

Maiuthed, Arnatchai; Chantarawong, Wipa; Chanvorachote, Pithi

doi:10.21873/anticanres.12663

Cited by 72 publications

(62 citation statements)

References 107 publications

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“…Recent studies have also put forward that Bufalin has inhibitory effect on cancer stem cells (CSCs). In many cancer samples, there are a few cell subsets which have stemness and they are called as cancer stem cells (CSCs) [31,32]. Cancer stem cells were first identified in acute myeloid leukemia [33] and were gradually discovered in solid tumors including gallbladder cancer, colorectal cancer, prostate cancer, breast cancer, pancreatic cancer, liver cancer, colorectal cancer and etc.…”

Section: Discussionmentioning

confidence: 99%

Anti-tumor Activity of Bufalin by Inhibiting c-MET Mediated MEK/ERK and PI3K/AKT Signaling Pathways in Gallbladder Cancer

Qian¹,

Su²,

Wang³

et al. 2020

J. Cancer

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Gallbladder cancer is one of the most common malignant tumors in the biliary tract. In recent years, the chemotherapy treatment for gallbladder carcinoma has exhibited obvious characteristics of drug resistance and insensitivity, and one of the main factors is the existence of cancer stem cells. Here in this study, the effect of Bufalin on gallbladder cancer (GBC-SD) cells and the related mechanism were studied. The results indicated that Bufalin could inhibit the growth of gallbladder carcinoma both in vivo and in vitro. According to the biological behavior analysis, Bufalin induced apoptosis, inhibited the propagation, migration and invasion of GBC-SD cells, and blocked cell cycle at the G2/M stage. Besides, Bufalin inhibited the tumor sphere formation capability of gallbladder carcinoma in matrigel, reduced the expression of multiple stemness-associated proteins, including Oct4, Sox2 and the stem cell-surface marker proteins CD133 and CD44. Western blot assay showed that Bufalin inhibited MEK/ERK and PI3-K/AKT signaling pathways by inhibiting the expression of p-c-Met, which in turn affected the expression of apoptosis-related protein Mcl-1, and the invasion-associated proteins E-cadherin, MMP9 and Snail. Bufalin was found to have an inhibitory effect on the GBC-SD cell growth and reduce the self-renewal and characteristic of gallbladder cancer stem cells. It enhanced the chemotherapeutic sensitivity and reduced the metastasis of gallbladder carcinoma. In conclusion, Bufalin can be used as a new promising anticancer drug for gallbladder cancer patients who are resistant to traditional chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Anti-tumor Activity of Bufalin by Inhibiting c-MET Mediated MEK/ERK and PI3K/AKT Signaling Pathways in Gallbladder Cancer

Qian¹,

Su²,

Wang³

et al. 2020

J. Cancer

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“…Due to poor diagnosis and chemotherapeutic responses, several published studies have attempted to discover new chemotherapeutic candidates from natural sources against lung cancer, particularly NSCLC [ 33 , 34 , 35 ]. Yellow and green pigments isolated from the seed oil of Calophyllum inophyllum L. was found to have tumoricidal activity against colon and lung cancers and potentiated gefitinib cytotoxicity [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Prodigiosin-Emerged PI3K/Beclin-1-Independent Pathway Elicits Autophagic Cell Death in Doxorubicin-Sensitive and -Resistant Lung Cancer

Chiu

Lin

Chen

et al. 2018

JCM

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Prodigiosin (PG) belongs to a family of prodiginines isolated from gram-negative bacteria. It is a water insoluble red pigment and a potent proapoptotic compound. This study elucidates the anti-tumor activity and underlying mechanism of PG in doxorubicin-sensitive (Dox-S) and doxorubicin-resistant (Dox-R) lung cancer cells. The cytotoxicity and cell death characteristics of PG in two cells were measured by MTT assay, cell cycle analysis, and apoptosis/autophagic marker analysis. Then, the potential mechanism of PG-induced cell death was evaluated through the phosphatidylinositol-4,5-bisphosphate 3-kinase-p85/Protein kinase B /mammalian target of rapamycin (PI3K-p85/Akt/mTOR) and Beclin-1/phosphatidylinositol-4,5-bisphosphate 3-kinase-Class III (Beclin-1/PI3K-Class III) signaling. Finally, in vivo efficacy was examined by intratracheal inoculation and treatment. There was similar cytotoxicity with PG in both Dox-S and Dox-R cells, where the half maximal inhibitory concentrations (IC50) were all in 10 μM. Based on a non-significant increase in the sub-G1 phase with an increase of microtubule-associated proteins 1A/1B light chain 3B-phosphatidylethanolamine conjugate (LC3-II), the cell death of both cells was categorized to achieve autophagy. Interestingly, an increase in cleaved-poly ADP ribose polymerase (cleaved-PARP) also showed the existence of an apoptosis-sensitive subpopulation. In both Dox-S and Dox-R cells, PI3K-p85/Akt/mTOR signaling pathways were reduced, which inhibited autophagy initiation. However, Beclin-1/PI3K-Class III downregulation implicated non-canonical autophagy pathways were involved in PG-induced autophagy. At completion of the PG regimen, tumors accumulated in the mice trachea and were attenuated by PG treatment, which indicated the efficacy of PG for both Dox-S and Dox-R lung cancer. All the above results concluded that PG is a potential chemotherapeutic agent for lung cancer regimens regardless of doxorubicin resistance.

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“…Here, we utilized the K-means clustering algorithm with high stem cell-like characteristics-associated lncRNAs to identify a unique subset of LUAD patients. These patients showed poor survival and lower expression differentiation markers such as DNAI1, NKX2-1, and SCGB1A1, and higher expression of stem cell markers such as ALDH1A1 and CD133 (37,49,50). The expressions of DNAI1, NKX2-1, and SCGB1A1 genes are required for the differentiation of many cell types, including secretory (club) cells (49,51,52).…”

Section: Discussionmentioning

confidence: 97%

A Greedy Algorithm-Based Stem Cell LncRNA Signature Identifies a Novel Subgroup of Lung Adenocarcinoma Patients With Poor Prognosis

et al. 2020

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Cancer stem cells play an essential role in therapy response and aggressiveness of various cancers, including lung adenocarcinoma (LUAD). Interestingly it also shares many features of embryonic stem cells (ESCs). Recently, long non-coding RNAs (lncRNAs) have emerged as a critical regulator of cell physiology. Here, we used expression data of ESCs, LUAD, and normal lung to identify 198 long non-coding hESC-associated lncRNAs (hESC-lncRNAs). Intriguingly, K-means clustering of hESC-associated lncRNAs identified a subgroup of LUAD patients [undifferentiated LUAD (uLUAD)] with high stem cell-like characteristic, decreased differentiation genes expression, and poor survival. We also observed that the uLUAD patients had overexpression of proteins associated with cell proliferation. Interestingly, uLUAD patients were highly enriched with the stemness-related gene sets, and had higher mutation load. A notable result observed was high infiltration of T cells and a higher level of neopeptides in uLUAD patients, making these patients an optimal candidate for immunotherapy. Further, feature selection using greedy algorithm identified 17-hESC-lncRNAs signature, which showed significant consistency with 198 hESC-lncRNAs-based classification, and identified a group of patients with high stem cell-like characteristic in the 10 most common cancer types and CCLE cell lines. These results suggest the conventional role of hESC-lncRNAs in stem cell biology. In summary, we identified a novel subgroup of LUAD patients (uLUAD) using a set of hESC-lncRNAs. The uLUAD patients had high stem cell-like characteristic and reduced survival rate and may be referred for immunotherapy. Furthermore, our analysis also showed the importance of lncRNAs in cancer and cancer stem cells.

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Lung Cancer Stem Cells and Cancer Stem Cell-targeting Natural Compounds

Cited by 72 publications

References 107 publications

Anti-tumor Activity of Bufalin by Inhibiting c-MET Mediated MEK/ERK and PI3K/AKT Signaling Pathways in Gallbladder Cancer

Anti-tumor Activity of Bufalin by Inhibiting c-MET Mediated MEK/ERK and PI3K/AKT Signaling Pathways in Gallbladder Cancer

Prodigiosin-Emerged PI3K/Beclin-1-Independent Pathway Elicits Autophagic Cell Death in Doxorubicin-Sensitive and -Resistant Lung Cancer

A Greedy Algorithm-Based Stem Cell LncRNA Signature Identifies a Novel Subgroup of Lung Adenocarcinoma Patients With Poor Prognosis

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