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Open AccessArticle

Ultrastructural and Morphological Effects in T-Lymphoblastic Leukemia CEM-SS Cells Following Treatment with Nordamnacanthal and Damnacanthal from Roots of Morinda elliptica

by Saiful Yazan Latifah, Banulata Gopalsamy, Raha Abdul Rahim, Abdul Manaf Ali and Nordin Haji Lajis

Molecules 2022, 27(13), 4136; https://doi.org/10.3390/molecules27134136 - 28 Jun 2022

Cited by 4 | Viewed by 2139

Abstract

Background: Morinda elliptica (family Rubiaceae), locally known as ‘mengkudu kecil’, has been used by the Malays for medicinal purposes. Anthraquinones isolated from the roots of Morinda elliptica, namely nordamnacanthal and damnacanthal, have been widely reported to exhibit anticancer and antioxidant properties in various cancer models in vitro and in vivo. Aim: This study analyzed the morphological and ultrastructural effects of damnacanthal and nordamnacanthal on T-lymphoblastic leukemia CEM-SS cells. Method: Light microscopy, Giemsa staining, Wright’s staining, scanning electron microscopy, and transmission electron microscopy were carried out to determine apoptosis, necrosis, and ultrastructural changes that occurred within the cells. Results: The outcomes showed that these compounds induced cell death by apoptosis and necrosis, specifically at higher doses of 10 and 30 μg/mL. Condensation and fragmentation of the nuclear chromatin, which further separated into small, membrane-bound vesicles known as apoptotic bodies, were observed in the nuclei and cytoplasm. The plasma membranes and cytoskeletons also showed marked morphological changes upon treatment with damnacanthal and nordamnacanthal, indicating apoptosis. Conclusion: Therefore, we report that damnacanthal and nordamnacanthal exhibit anticancer properties by inducing apoptosis and necrosis in CEM-SS cells, and they have potential as a drug for the treatment of T-lymphoblastic leukemia. Full article

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20 pages, 7962 KB

Open AccessArticle

Anticancer Potential of Damnacanthal and Nordamnacanthal from Morinda elliptica Roots on T-lymphoblastic Leukemia Cells

by Saiful Yazan Latifah, Banulata Gopalsamy, Raha Abdul Rahim, Abdul Manaf Ali and Nordin Haji Lajis

Molecules 2021, 26(6), 1554; https://doi.org/10.3390/molecules26061554 - 12 Mar 2021

Cited by 17 | Viewed by 3220

Abstract

Background: This study reports on the cytotoxic properties of nordamnacanthal and damnacanthal, isolated from roots of Morinda elliptica on T-lymphoblastic leukaemia (CEM-SS) cell lines. Methods: MTT assay, DNA fragmentation, ELISA and cell cycle analysis were carried out. Results: Nordamnacanthal and damnacanthal at IC₅₀ values of 1.7 μg/mL and10 μg/mL, respectively. At the molecular level, these compounds caused internucleosomal DNA cleavage producing multiple 180–200 bp fragments that are visible as a “ladder” on the agarose gel. This was due to the activation of the Mg²⁺/Ca²⁺-dependent endonuclease. The induction of apoptosis by nordamnacanthal was different from the one induced by damnacanthal, in a way that it occurs independently of ongoing transcription process. Nevertheless, in both cases, the process of dephosphorylation of protein phosphates 1 and 2A, the ongoing protein synthesis and the elevations of the cytosolic Ca²⁺ concentration were not needed for apoptosis to take place. Nordamnacanthal was found to have a cytotoxic effect by inducing apoptosis, while damnacanthal caused arrest at the G0/G1 phase of the cell cycle. Conclusion: Damnacanthal and nordamnacanthal have anticancer properties, and could act as potential treatment for T-lymphoblastic leukemia. Full article

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15 pages, 2970 KB

Open AccessArticle

Combinatorial Cytotoxic Effects of Damnacanthal and Doxorubicin against Human Breast Cancer MCF-7 Cells in Vitro

by Muhammad Yusran Abdul Aziz, Nadiah Abu, Swee Keong Yeap, Wan Yong Ho, Abdul Rahman Omar, Nor Hadiani Ismail, Syahida Ahmad, Mehdi R. Pirozyan, Nadeem M. Akhtar and Noorjahan Banu Alitheen

Molecules 2016, 21(9), 1228; https://doi.org/10.3390/molecules21091228 - 14 Sep 2016

Cited by 29 | Viewed by 7243

Abstract

Despite progressive research being done on drug therapy to treat breast cancer, the number of patients succumbing to the disease is still a major issue. Combinatorial treatment using different drugs and herbs to treat cancer patients is of major interest in scientists nowadays. Doxorubicin is one of the most used drugs to treat breast cancer patients. The combination of doxorubicin to other drugs such as tamoxifen has been reported. Nevertheless, the combination of doxorubicin with a natural product-derived agent has not been studied yet. Morinda citrifolia has always been sought out for its remarkable remedies. Damnacanthal, an anthraquinone that can be extracted from the roots of Morinda citrifolia is a promising compound that possesses a variety of biological properties. This study aimed to study the therapeutic effects of damnacanthal in combination with doxorubicin in breast cancer cells. Collectively, the combination of both these molecules enhanced the efficacy of induced cell death in MCF-7 as evidenced by the MTT assay, cell cycle, annexin V and expression of apoptosis-related genes and proteins. The effectiveness of doxorubicin as an anti-cancer drug was increased upon addition of damnacanthal. These results could provide a promising approach to treat breast cancer patients. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 317 KB

Open AccessCommunication

Total Synthesis, Cytotoxic Effects of Damnacanthal, Nordamnacanthal and Related Anthraquinone Analogues

by Muhammad Nadeem Akhtar, Seema Zareen, Swee Keong Yeap, Wan Yong Ho, Kong Mun Lo, Aurangzeb Hasan and Noorjahan Banu Alitheen

Molecules 2013, 18(8), 10042-10055; https://doi.org/10.3390/molecules180810042 - 20 Aug 2013

Cited by 28 | Viewed by 12580

Abstract

Naturally occurring anthraquinones, damnacanthal (1) and nordamnacanthal (2) were synthesized with modified reaction steps and investigated for their cytotoxicity against the MCF-7 and K-562 cancer cell lines, respectively. Intermediate analogues 2-bromomethyl-1,3-dimethoxyanthraquinone (5, IC₅₀ = 5.70 ± 0.21 and 8.50 ± 1.18 mg/mL), 2-hydroxymethyl-1,3-dimethoxyanthraquinone (6, IC₅₀ = 12.10 ± 0.14 and 14.00 ± 2.13), 2-formyl-1,3-dimethoxyantharquinone (7, IC₅₀ = 13.10 ± 1.02 and 14.80 ± 0.74), 1,3-dimethoxy-2-methylanthraquinone (4, IC₅₀ = 9.40 ± 3.51 and 28.40 ± 2.33), and 1,3-dihydroxy-2-methylanthraquinone (3, IC₅₀ = 25.60 ± 0.42 and 28.40 ± 0.79) also exhibited moderate cytotoxicity against MCF-7 and K-562 cancer cell lines, respectively. Other structurally related compounds like 1,3-dihydroxyanthraquinone (13a, IC₅₀ = 19.70 ± 0.35 and 14.50 ± 1.28), 1,3-dimethoxyanthraquinone (13b, IC₅₀ = 6.50 ± 0.66 and 5.90 ± 0.95) were also showed good cytotoxicity. The target compound damnacanthal (1) was found to be the most cytotoxic against the MCF-7 and K-562 cancer cell lines, with IC₅₀ values of 3.80 ± 0.57 and 5.50 ± 1.26, respectively. The structures of all compounds were elucidated with the help of detailed spectroscopic techniques. Full article

(This article belongs to the Section Organic Chemistry)

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9 pages, 222 KB

Open AccessArticle

Anthraquinones with Antiplasmodial Activity from the Roots of Rennellia elliptica Korth. (Rubiaceae)

by Che Puteh Osman, Nor Hadiani Ismail, Rohaya Ahmad, Norizan Ahmat, Khalijah Awang and Faridahanim Mohd Jaafar

Molecules 2010, 15(10), 7218-7226; https://doi.org/10.3390/molecules15107218 - 20 Oct 2010

Cited by 54 | Viewed by 11766

Abstract

Dichloromethane root extract of Rennellia elliptica Korth. showed strong inhibition of Plasmodium falciparum growth in vitro with an IC₅₀value of 4.04 µg/mL. A phytochemical study of the dichloromethane root extract has led to the isolation and characterization of a new anthraquinone, 1,2-dimethoxy-6-methyl-9,10-anthraquinone (1), and ten known anthraquinones: 1-hydroxy-2-methoxy-6-methyl-9,10-anthraquinone (2), nordamnacanthal (3), 2-formyl-3-hydroxy-9,10-anthraquinone (4), damnacanthal (5), lucidin-ω-methyl ether (6), 3-hydroxy-2-methyl-9,10-anthraquinone (7), rubiadin (8), 3-hydroxy-2-methoxy-6-methyl-9,10-anthraquinone (9), rubiadin-1-methyl ether (10) and 3-hydroxy-2-hydroxymethyl-9,10-anthraquinone (11). Structural elucidation of all compounds was accomplished by modern spectroscopic methods, notably 1D and 2D NMR, IR, UV and HREIMS. The new anthraquinone 1, 2-formyl-3-hydroxy-9,10-anthraquinone (4) and 3-hydroxy-2-methyl-9,10-anthraquinone (7) possess strong antiplasmodial activity, with IC₅₀ values of 1.10, 0.63 and 0.34 µM, respectively. Full article

(This article belongs to the Section Natural Products Chemistry)

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